Patients with kidney disease suffer from the adverse effects of toxin build-up in their blood. Dialysis is a process which employs an artificial kidney to remove those toxins. In hemodialysis a dialyzer is used which contains a semi-permeable membrane dividing the dialyzer into two chambers. Blood is pumped through one chamber and a dialysis solution through the second. As the blood flows by the dialysis fluid, separated by the semipermeable membrane, blood impurities such as urea and creatinine diffuse through the semi-permeable membrane into the dialysis solution by the diffusion, convection and absorption. The electrolyte concentration of the dialysis fluid is set so as to maintain electrolytic balance within the patient.
The semi-permeable membrane is often a large number of microfibers encased in a chamber. The chamber is often a hollow cylinder open at both ends. Thousands of hollow semipermeable microfibers carry blood from one end to the opposite end so that blood flows through the microfibers in a first direction. Dialysate ports are also present on opposite ends of the chamber. One port carries dialysate into the chamber, the dialysate flows through the chamber in a countercurrent direction to the blood flow, and the other port carries the dialysate out of the chamber. The solute removal thus takes place across the semipermeable membrane that is the microfiber wall. This design produces a high surface area for solute removal in a relatively low volume device.
One significant challenge is to connect the microfiber interior channels to the blood lines, so that blood flows smoothly from the arterial blood line, into the microfiber interior channels where it can pass into and through the dialyzer chamber, and out the other end of the microfiber interior channels to the venous blood line.
This is done by potting the microfiber ends with a potting material. The potting material encases the microfiber ends to seal them from the chamber interior and to hold them in position within the chamber. The end result is a dialyzer in a generally cylindrical shape with a hollow interior chamber. Ports at each end of the chamber allow passage of dialysate therethrough. Within the chamber are the microfibers, positioned longitudinally so that their ends extend to the respective chamber ends. The blood passes through the lumens of the microfibers in the opposite direction from the direction of dialysate movement through the dialyzer chamber. The blood is thus separated from the dialyzer by the microfiber walls. At each end of the chamber, the microfiber lumens are open to the exterior of the dialyzer, which is fitted with the blood lines to carry blood between the dialyzer and the patient. The microfibers are held in place, and the dialyzer chamber is sealed from its ends, by the potting material.
This potting material is typically epoxy or urethane. It is injected into the dialysate ports on each end of the chamber, and the dialyzer is spun in a centrifuge. The centripetal force produced by the rotation in the centrifuge forces the potting material to each end, where it sets and hardens.
One of the manufacturing steps for a dialyzer, like many other medical devices that come into contact with body fluid, is sterilization. It is important that the dialyzer be free of pathogens that could migrate into the blood flowing through the microfiber lumens and thereby enter the patient's bloodstream.
A common method of sterilizing medical devices is by heated steam in an autoclave. Hot steam is introduced to kill pathogens to an acceptable level, and then the steam is removed and the device is allowed to cool. The removal of the steam is facilitated by a vacuum drying cycle; a vacuum is applied which draws off the remaining steam and any condensate.
It has been discovered that steam autoclaving as a method for sterilizing a dialyzer can affect the structural integrity of the dialyzer. Specifically, dialyzers subjected to steam autoclaving often show delamination between the potting material used to pot the microfibers in place and the dialyzer housing. The result may be a gap between the potting material or at least a structural discontinuity.
Investigation reveals that the reason for this delamination effect upon steam autoclaving may be two-fold. First, the potting material and the dialyzer housing typically have different coefficients of thermal expansion because they are made of different types of materials. The potting material is commonly a polyurethane, while the dialyzer housing is commonly a polycarbonate. The decrease in temperature at the end of autoclaving produces differential shrinkage between the two materials. This differential shrinkage produces strain at the interface between the materials which, at least in some cases, causes delamination or structural discontinuities.
Second, investigation suggests that the rate of cooling is different in the potting as compared to the dialyzer housing. This appears to be a result of evaporative cooling in the potting material. Autoclave steam condenses or collects to some extent on the surfaces of the dialyzer. Condensate not only collects but also is absorbed into the absorptive microfibers. Upon application of the drying vacuum, the condensate evaporates at different rates from the absorptive material of the microfibers compared to the nonabsorptive materials. The condensate evaporates fastest from the nonabsorptive material, since all the condensate is at the surface and can freely vaporize into the partial vacuum. In comparison, the condensate evaporates into the partial vacuum slower from the absorptive material of the microfibers, because some of the condensate must migrate from the interior of the material to the exterior surface where the molecules can evaporate.
Because the condensate evaporates slowest from the absorptive microfibers, and perhaps because the absorptive microfibers hold a relatively large amount of condensate, they stay moist the longest. At a point in the vacuum drying process, the nonabsorptive surfaces will be essentially dry while the absorptive microfibers are still moist. Continued application of the vacuum drying process beyond this point is necessary to dry the microfibers. At this stage, there is little or no evaporative cooling effect on the dry nonabsorptive surfaces, but there continues to be an evaporative cooling effect on the absorptive microfibers.
This differential evaporation produces differential cooling between the absorptive microfibers and the nonabsorptive materials. Early in the vacuum drying, when there is still condensate on the nonabsorptive materials, they experience relatively large rates of evaporation and consequently relatively rapid cooling. However, this cooling, while rapid, is very short-lived because the nonabsorptive materials have very little condensate on them to begin with. Later in the vacuum drying process, after the nonabsorptive material is essentially dry, the nonabsorptive material experiences relatively no evaporation and consequently relatively slow cooling.
In a typical scenario, the temperature gradients are as follows. The temperature of the entire dialyzer is high and uniform at the conclusion of the steam autoclaving. Upon application of the vacuum dryer process, the temperature of the nonabsorptive materials initially falls quickly to a temperature less than that of the absorptive microfiber due to rapid evaporation from those materials. Once the condensate is fully evaporated from the nonabsorptive materials, however, the temperature of the nonabsorptive materials stabilizes. Continued evaporation from the absorptive materials continues to cool them, so that their temperature becomes as low as the temperature of the nonabsorptive materials, and then even lower.
These temperature gradients due to differential evaporative cooling are mitigated slightly but not fully by other cooling mechanisms. For example, both the nonabsorptive materials and the absorptive materials cool by radiation. They also cool by conduction; that is, the surfaces lose heat to colliding molecules that pass by. This conductive cooling is of little effect, however, since it operates in a high vacuum; there simply are too few passing molecules.
The temperature difference in the absorptive microfibers, as described above, is reflected as well in the potting material into which they are potted. In other words, due to heat conduction through the potting material and the microfibers, the potting material tends to be warmer than the other nonabsorptive materials early in the vacuum drying. Later in the vacuum drying, the potting material tends to be cooler than the other nonabsorptive materials. This appears to be a significant reason for the differential cooling—and resulting differential shrinkage—between the dialyzer housing and the potting material during vacuum drying.